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1.
Colloids Surf B Biointerfaces ; 238: 113887, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581835

RESUMO

Alzheimer's disease (AD) is complex and multifactorial, and its pathogenesis involves multiple factors and processes. This study pioneered the in situ growth of cerium oxide nanoparticles on macrophage membranes (Ce-RAW). Further, carbon quantum dots (CQD) were biomimetically modified by Ce-RAW, leading to the synthesis of a multifunctional nanocomposite (CQD-Ce-RAW). Within the framework of this research, CQD-Ce-RAW was strategically combined with photothermal therapy (PTT), aiming to achieve a more significant therapeutic effect. The macrophage membrane confers the system with anti-phagocytic and anti-inflammatory biological functions. More importantly, the ultra-small size of cerium oxide grown on the membrane acts as a reactive oxygen species (ROS) scavenger and alleviates the degree of oxidative stress. Meanwhile, CQD as a photosensitizer helps dissociate amyloid-ß (Aß) aggregates and chelates excess copper ions, thus further inhibiting Aß aggregation. Cell experiments showed that CQD-Ce-RAW combined with PTT could effectively degrade and inhibit the aggregation of Aß, remove ROS, and improve cell survival rate. The results of in vivo photothermal experiments demonstrated that near-infrared light enhanced the efficiency of drug penetration through the blood-brain barrier and facilitated its accumulation in brain tissue. This comprehensive therapeutic approach can intervene in the disease progression from multiple pathways, providing a new prospect for treating AD.


Assuntos
Doença de Alzheimer , Biofilmes , Cério , Nanopartículas , Terapia Fototérmica , Espécies Reativas de Oxigênio , Cério/química , Cério/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/terapia , Doença de Alzheimer/patologia , Animais , Camundongos , Nanopartículas/química , Biofilmes/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Pontos Quânticos/química , Peptídeos beta-Amiloides/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Tamanho da Partícula , Células RAW 264.7 , Humanos , Propriedades de Superfície , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos
2.
Adv Healthc Mater ; 13(6): e2303211, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37947289

RESUMO

The complex pathological mechanism of Alzheimer's disease (AD) limits the efficacy of simple drug therapy, and drugs are difficult to penetrate the blood-brain barrier (BBB). Therefore, it is a breakthrough to enhance the therapeutic effect of AD by rationally using multiple therapeutic strategies to inhibit multiple pathological targets. In this study, macrophage membrane (MM) with active targeting inflammation function is used to functionalize molybdenum disulfide quantum dots (MoS2 QDs) with the properties of elimination of reactive oxygen species (ROS) and anti-Aß1-42 deposition to form the nano drug (MoS2 QDs/MM), and play the role of multi-target combined therapy with NIR. The results show that MoS2 QDs/MM has a targeted therapeutic effect on ROS elimination and anti-deposition of Aß1-42 . In addition, the combined therapy group effectively reduced Aß1-42 mediated cytotoxicity. The modification of MM could effectively target the brain, and NIR irradiation could actively increase the cross of BBB of materials. In vivo behavioral study also show that APP/PS1 mice in the combined treatment group showed the similar exploration desire and learning ability to mice in the group of WT. MoS2 QDs/MM is an excellent nano drug with multiple effects, which has advantages in the field of neurological diseases with crisscross pathogenesis.


Assuntos
Doença de Alzheimer , Dissulfetos , Pontos Quânticos , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Molibdênio/farmacologia , Espécies Reativas de Oxigênio , Macrófagos
3.
Int J Nanomedicine ; 18: 2163-2180, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37131544

RESUMO

Due to the aging of the global population, the burden of bone-related diseases has increased sharply. Macrophage, as indispensable components of both innate immune responses and adaptive immunity, plays a considerable role in maintaining bone homeostasis and promoting bone establishment. Small extracellular vesicles (sEVs) have attracted increasing attention because they participate in cell cross-talk in pathological environments and can serve as drug delivery systems. In recent years, an increasing number of studies have expanded our knowledge about the effects of macrophage-derived sEVs (M-sEVs) in bone diseases via different forms of polarization and their biological functions. In this review, we comprehensively describe on the application and mechanisms of M-sEVs in various bone diseases and drug delivery, which may provide new perspectives for treating and diagnosing human bone disorders, especially osteoporosis, arthritis, osteolysis, and bone defects.


Assuntos
Vesículas Extracelulares , Osteólise , Osteoporose , Humanos , Macrófagos , Imunidade Inata
4.
J Orthop Surg Res ; 18(1): 294, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37041549

RESUMO

BACKGROUND: To compare the biomechanical properties and stability, using a finite element model, of four fixation constructs used for the treatment of anterior column and posterior hemi-transverse (ACPHT) acetabular fractures under two physiological loading conditions (standing and sitting). METHODS: A finite element model simulating ACPHT acetabular fractures was created for four different scenarios: a suprapectineal plate combined with posterior column and infra-acetabular screws (SP-PS-IS); an infrapectineal plate combined with posterior column and infra-acetabular screws (IP-PS-IS); a special infrapectineal quadrilateral surface buttress plate (IQP); and a suprapectineal plate combined with a posterior column plate (SP-PP). Three-dimensional finite element stress analysis was performed on these models with a load of 700 N in standing and sitting positions. Biomechanical stress distributions and fracture displacements were analysed and compared between these fixation techniques. RESULTS: In models simulating the standing position, high displacements and stress distributions were observed at the infra-acetabulum regions. The degree of these fracture displacements was low in the IQP (0.078 mm), as compared to either the IP-PS-IS (0.079 mm) or the SP & PP (0.413 mm) fixation constructs. However, the IP-PS-IS fixation construct had the highest effective stiffness. In models simulating the sitting position, high fracture displacements and stress distributions were observed at the regions of the anterior and posterior columns. The degree of these fracture displacements was low in the SP-PS-IS (0.101 mm), as compared to the IP-PS-IS (0.109 mm) and the SP-PP (0.196 mm) fixation constructs. CONCLUSION: In both standing and sitting positions, the stability and stiffness index were comparable between the IQP, SP-PS-IS, and IP-PS-IS. These 3 fixation constructs had smaller fracture displacements than the SP-PP construct. The stress concentrations at the regions of quadrilateral surface and infra-acetabulum suggest that the buttressing fixation of quadrilateral plate was required for ACPHT fractures.


Assuntos
Fraturas do Quadril , Fraturas da Coluna Vertebral , Humanos , Fixação Interna de Fraturas/métodos , Análise de Elementos Finitos , Fenômenos Biomecânicos , Parafusos Ósseos
5.
Hum Genomics ; 17(1): 33, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-37004060

RESUMO

BACKGROUND: Super-enhancers (SEs), driving high-level expression of genes with tumor-promoting functions, have been investigated recently. However, the roles of super-enhancer-associated lncRNAs (SE-lncRNAs) in tumors remain undetermined, especially in gliomas. We here established a SE-lncRNAs expression-based prognostic signature to choose the effective treatment of glioma and identify a novel therapeutic target. METHODS: Combined analysis of RNA sequencing (RNA-seq) data and ChIP sequencing (ChIP-seq) data of glioma patient-derived glioma stem cells (GSCs) screened SE-lncRNAs. Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets served to construct and validate SE-lncRNA prognostic signature. The immune profiles and potential immuno- and chemotherapies response prediction value of the signature were also explored. Moreover, we verified the epigenetic activation mechanism of LINC00945 via the ChIP assay, and its effect on glioma was determined by performing the functional assay and a mouse xenograft model. RESULTS: 6 SE-lncRNAs were obtained and identified three subgroups of glioma patients with different prognostic and clinical features. A risk signature was further constructed and demonstrated to be an independent prognostic factor. The high-risk group exhibited an immunosuppressive microenvironment and was higher enrichment of M2 macrophage, regulatory T cells (Tregs), and Cancer-associated fibroblasts (CAFs). Patients in the high-risk group were better candidates for immunotherapy and chemotherapeutics. The SE of LINC00945 was further verified via ChIP assay. Mechanistically, BRD4 may mediate epigenetic activation of LINC00945. Additionally, overexpression of LINC00945 promoted glioma cell proliferation, EMT, migration, and invasion in vitro and xenograft tumor formation in vivo. CONCLUSION: Our study constructed the first prognostic SE-lncRNA signature with the ability to optimize the choice of patients receiving immuno- and chemotherapies and provided a potential therapeutic target for glioma.


Assuntos
Glioma , RNA Longo não Codificante , Humanos , Animais , Camundongos , Prognóstico , RNA Longo não Codificante/genética , Proteínas Nucleares , Fatores de Transcrição , Glioma/genética , Modelos Animais de Doenças , Microambiente Tumoral/genética , Proteínas de Ciclo Celular
6.
J Orthop Surg Res ; 18(1): 35, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635756

RESUMO

BACKGROUND: Reports on traumatic sciatic nerve injury associated with acetabular fracture are rare. In this study, we investigated the demographics of these injuries, their clinical characteristics, management, and factors potentially influencing neurological recovery. METHODS: We retrospectively reviewed all patients diagnosed to have acetabular fracture at our trauma center between January 2014 and June 2021. Data on patient demographics, characteristics of sciatic nerve injury, neurological recovery, factors potentially influencing neurological recovery were analyzed. RESULTS: Eighteen patients (bilateral in one case) met the diagnostic criteria. All these injuries involved the posterior wall or posterior column, and most patients had posterior dislocation of the hip joint. Four of the 19 sides with traumatic sciatic nerve injury involved the common peroneal nerve division and 15 involved both the common peroneal and tibial nerve divisions. Seventeen patients (18 sides) underwent intraoperative nerve exploration, which revealed abnormalities in 7 sides and no obvious abnormality in 11 sides. At the last follow-up, 10 sides (52.6%) had complete recovery and 9 (47.4%) had partial recovery; the difference was statistically significant between those with or without abnormal nerve damage during exploration (P = 0.046). Linear regression analysis showed that a nerve abnormality detected intraoperatively was a predictor of nerve recovery (P = 0.009). The mean recovery time was significantly longer for partial recovery than for complete recovery (13.78 months vs. 6.70 months; P = 0.001). CONCLUSIONS: All the injuries in this series involved the posterior wall or posterior column, and most patients had posterior dislocation of the hip joint. Damage to the common peroneal nerve division was more severe than that to the tibial nerve division preoperatively. However, the degree of recovery of the common peroneal division was not worse than that of the tibial division. There was a relationship between the degree of neurological recovery and whether there was an abnormality at the time of intraoperative nerve exploration. Patients with partial recovery took longer to recover.


Assuntos
Fraturas do Quadril , Luxações Articulares , Traumatismos dos Nervos Periféricos , Fraturas da Coluna Vertebral , Humanos , Estudos Retrospectivos , Incidência , Acetábulo/cirurgia , Acetábulo/lesões , Fraturas do Quadril/cirurgia , Traumatismos dos Nervos Periféricos/epidemiologia , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/cirurgia , Nervo Fibular , Nervo Isquiático , Resultado do Tratamento
7.
Cell Mol Bioeng ; 15(6): 599-609, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36531863

RESUMO

Introduction: Cdc42 has been linked to multiple human cancers and is implicated in the migration of cancer cells. Cdc42 could be activated via biochemical and biophysical factors in tumor microenvironment, the precise control of Cdc42 was essential to determine its role to cell behaviors. Needle-shaped protrusions (filopodia) could sense the extracellular biochemical cues and pave the path for cell movement, which was a key structure involved in the regulation of cancer cell motility. Methods: We used the photoactivatable Cdc42 to elucidate the breast cancer cell protrusions, the mutation of Cdc42 was to confirm the optogenetic results. We also inhibit the Cdc42, Rac or Rho respectively by the corresponding inhibitors. Results: We identified that the activation of Cdc42 by light could greatly enhance the formation of filopodia, which was positive for the contribution of cell movement. The expression of Cdc42 active form Cdc42-Q61L in cells resulted in the longer and more filopodia while the Cdc42 inactive form Cdc42-T17N were with the shorter and less filopodia. Moreover, the inhibition of Cdc42, Rac or Rho all significantly reduced the filopodia numbers and length in the co-expression of Cdc42-Q61L, which showed that the integration of small GTPases was necessary in the formation of filopodia. Furthermore, photoactivation of Cdc42 failed to enhance the filopodia formation with the inhibition of Rac or Rho. However, with the inhibition of Cdc42, the photoactivation of Cdc42 could partially recover back the filopodia formations, which indicated that the integration of small GTPases was key for the filopodia formations. Conclusions: Our work highlights that light activates Cdc42 is sufficient to promote filopodia formation without the destructive structures of small GTPases, it not only points out the novel technique to determine cell structure formations but also provides the experimental basis for the efficient small GTPases-based anti-cancer strategies.

8.
Epigenomics ; 14(18): 1089-1104, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36222052

RESUMO

Aim: To explore the prognostic value of methylated snoRNA genes in glioma and construct a prognostic risk signature. Materials & methods: We retrieved clinical information and 450K methylation data from The Cancer Genome Atlas and obtained five methylated snoRNA genes. Then we established a risk signature and verified the effect of SNORA71B on glioma cells with functional assays. Results: A risk signature containing five methylated snoRNA genes was constructed and demonstrated to be an independent predictor of glioma prognosis. Silencing SNORA71B restrained the proliferation, migration and invasion of glioma cells and reduced the expression of mesenchymal and cell cycle marker proteins. Conclusion: This study constructed a methylated snoRNA gene risk signature, which may provide a reference for glioma patients' prognosis assessment.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Proteínas de Ciclo Celular , Glioma/genética , Glioma/metabolismo , Humanos , Prognóstico , RNA Nucleolar Pequeno/genética
9.
Front Oncol ; 12: 930923, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847925

RESUMO

Gliomas are a group of the most aggressive primary central nervous system tumors with limited treatment options. The abnormal expression of long non-coding RNA (lncRNA) is related to the prognosis of glioma. However, the role of endoplasmic reticulum (ER) stress-associated lncRNAs in glioma prognosis has not been reported. In this paper, we obtained ER stress-related lncRNAs by co-expression analysis, and then a risk signature composed of 6 ER stress-related lncRNAs was constructed using Cox regression analysis. Glioma samples in The Cancer Genome Atlas (TCGA) were separated into high- and low-risk groups based on the median risk score. Compared with the low-risk group, patients in the high-risk group had shorter survival times. Additionally, we verified the predictive ability of these candidate lncRNAs in the testing set. Three glioma patient subgroups (cluster 1/2/3) were identified by consensus clustering. We further analysed the abundance of immune-infiltrating cells and the expression levels of immune checkpoint molecules in both three subgroups and two risk groups, respectively. Immunotherapy and anticancer drug response prediction showed that ER stress-related lncRNA risk signature positively correlates with responding to immune checkpoints and chemosensitivity. Functional analysis showed that these gene sets are enriched in the malignant process of tumors. Finally, LINC00519 was chosen for functional experiments. The silence of LINC00519 restrained the migration and invasion of glioma cells. Hence, those results indicated that ER stress-related lncRNA risk signature could be a potential treatment target and a prognosis biomarker for glioma patients.

10.
BMC Neurol ; 22(1): 192, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35614390

RESUMO

BACKGROUND: Glioma is the most common brain tumor in adults and is characterized by a short survival time and high resistance to chemotherapy. It is imperative to determine the prognosis and therapy-related targets for glioma. Endoplasmic reticulum stress (ERS), as an adaptive protective mechanism, indicates the unfolded protein response (UPR) to determine cell survival and affects chemotherapy sensitivity, which is related to the prognosis of glioma. METHODS: Our research used the TCGA database as the training group and the CGGA database as the testing group. Lasso regression and Cox analysis were performed to construct an ERS signature-based risk score model in glioma. Three methods (time-dependent receiver operating characteristic analysis and multivariate and univariate Cox regression analysis) were applied to assess the independent prognostic effect of texture parameters. Consensus clustering was used to classify the two clusters. In addition, functional and immune analyses were performed to assess the malignant process and immune microenvironment. Immunotherapy and anticancer drug response prediction were adopted to evaluate immune checkpoint and chemotherapy sensitivity. RESULTS: The results revealed that the 7-gene signature strongly predicts glioma prognosis. The two clusters have markedly distinct molecular and prognostic features. The validation group result revealed that the signature has exceptional repeatability and certainty. Functional analysis showed that the ERS-related gene signature was closely associated with the malignant process and prognosis of tumors. Immune analysis indicated that the ERS-related gene signature is strongly related to immune infiltration. Immunotherapy and anticancer drug response prediction indicated that the ERS-related gene signature is positively correlated with immune checkpoint and chemotherapy sensitivity. CONCLUSIONS: Collectively, the ERS-related risk model can provide a novel signature to predict glioma prognosis and treatment.


Assuntos
Neoplasias Encefálicas , Glioma , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Estresse do Retículo Endoplasmático , Glioma/genética , Glioma/metabolismo , Glioma/terapia , Humanos , Prognóstico , Fatores de Risco , Microambiente Tumoral/genética
11.
Front Oncol ; 12: 717926, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433410

RESUMO

Pyroptosis, a form of programmed cell death, that plays a significant role in the occurrence and progression of tumors, has been frequently investigated recently. However, the prognostic significance and therapeutic value of pyroptosis in glioma remain undetermined. In this research, we revealed the relationship of pyroptosis-related genes to glioma by analyzing whole transcriptome data from The Cancer Genome Atlas (TCGA) dataset serving as the training set and the Chinese Glioma Genome Atlas (CGGA) dataset serving as the validation set. We identified two subgroups of glioma patients with disparate prognostic and clinical features by performing consensus clustering analysis on nineteen pyroptosis-related genes that were differentially expressed between glioma and normal brain tissues. We further derived a risk signature, using eleven pyroptosis-related genes, that was demonstrated to be an independent prognostic factor for glioma. Furthermore, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to implement functional analysis of our gene set, and the results were closely related to immune and inflammatory responses in accordance with the characteristics of pyroptosis. Moreover, Gene Set Enrichment Analysis (GSEA) results showed that that the high-risk group exhibited enriched characteristics of malignant tumors in accordance with its poor prognosis. Next, we analyzed different immune cell infiltration between the two risk groups using ssGSEA. Finally, CASP1 was identified as a core gene, so we subsequently selected an inhibitor targeting CASP1 and simulated molecular docking. In addition, the inhibitory effect of belnacasan on glioma was verified at the cellular level. In conclusion, pyroptosis-related genes are of great significance for performing prognostic stratification and developing treatment strategies for glioma.

12.
Front Oncol ; 11: 736654, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671558

RESUMO

BACKGROUND: Accurate diagnosis of bone metastasis status of prostate cancer (PCa) is becoming increasingly more important in guiding local and systemic treatment. Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) have increasingly been utilized globally to assess the bone metastases in PCa. Our meta-analysis was a high-volume series in which the utility of PET/CT with different radioligands was compared to MRI with different parameters in this setting. MATERIALS AND METHODS: Three databases, including Medline, Embase, and Cochrane Library, were searched to retrieve original trials from their inception to August 31, 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The methodological quality of the included studies was assessed by two independent investigators utilizing Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). A Bayesian network meta-analysis was performed using an arm-based model. Absolute sensitivity and specificity, relative sensitivity and specificity, diagnostic odds ratio (DOR), and superiority index, and their associated 95% confidence intervals (CI) were used to assess the diagnostic value. RESULTS: Forty-five studies with 2,843 patients and 4,263 lesions were identified. Network meta-analysis reveals that 68Ga-labeled prostate membrane antigen (68Ga-PSMA) PET/CT has the highest superiority index (7.30) with the sensitivity of 0.91 and specificity of 0.99, followed by 18F-NaF, 11C-choline, 18F-choline, 18F-fludeoxyglucose (FDG), and 18F-fluciclovine PET/CT. The use of high magnetic field strength, multisequence, diffusion-weighted imaging (DWI), and more imaging planes will increase the diagnostic value of MRI for the detection of bone metastasis in prostate cancer patients. Where available, 3.0-T high-quality MRI approaches 68Ga-PSMA PET/CT was performed in the detection of bone metastasis on patient-based level (sensitivity, 0.94 vs. 0.91; specificity, 0.94 vs. 0.96; superiority index, 4.43 vs. 4.56). CONCLUSIONS: 68Ga-PSMA PET/CT is recommended for the diagnosis of bone metastasis in prostate cancer patients. Where available, 3.0-T high-quality MRI approaches 68Ga-PSMA PET/CT should be performed in the detection of bone metastasis.

13.
Front Oncol ; 11: 726745, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540695

RESUMO

Glioma is well known as the most aggressive and prevalent primary malignant tumor in the central nervous system. Molecular subtypes and prognosis biomarkers remain a promising research area of gliomas. Notably, the aberrant expression of mesenchymal (MES) subtype related long non-coding RNAs (lncRNAs) is significantly associated with the prognosis of glioma patients. In this study, MES-related genes were obtained from The Cancer Genome Atlas (TCGA) and the Ivy Glioblastoma Atlas Project (Ivy GAP) data sets of glioma, and MES-related lncRNAs were acquired by performing co-expression analysis of these genes. Next, Cox regression analysis was used to establish a prognostic model, that integrated ten MES-related lncRNAs. Glioma patients in TCGA were divided into high-risk and low-risk groups based on the median risk score; compared with the low-risk groups, patients in the high-risk group had shorter survival times. Additionally, we measured the specificity and sensitivity of our model with the ROC curve. Univariate and multivariate Cox analyses showed that the prognostic model was an independent prognostic factor for glioma. To verify the predictive power of these candidate lncRNAs, the corresponding RNA-seq data were downloaded from the Chinese Glioma Genome Atlas (CGGA), and similar results were obtained. Next, we performed the immune cell infiltration profile of patients between two risk groups, and gene set enrichment analysis (GSEA) was performed to detect functional annotation. Finally, the protective factors DGCR10 and HAR1B, and risk factor SNHG18 were selected for functional verification. Knockdown of DGCR10 and HAR1B promoted, whereas knockdown of SNHG18 inhibited the migration and invasion of gliomas. Collectively, we successfully constructed a prognostic model based on a ten MES-related lncRNAs signature, which provides a novel target for predicting the prognosis for glioma patients.

14.
Ecotoxicol Environ Saf ; 215: 112108, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33799132

RESUMO

Fluoride which is widespread in our environment and food due to its geological origin and industrial pollution has been identified as a developmental neurotoxicant. Gut-brain axis provides new insight into brain-derived injury. We previously found the psychoactive effects of a probiotic strain, Lactobacillus johnsonii BS15 against fluoride-induced memory dysfunction in mice by modulating the gut-brain axis. In this study, we aimed to detect the link between the reconstruction of gut microbiota and gut-brain axis through which probiotic alleviate fluoride-induced memory impairment. We also added an hour of water avoidance stress (WAS) before behavioral tests and sampling, aiming to demonstrate the preventive effects of the probiotic on fluoride-induced memory impairment after psychological stress. Mice were given fluoridated drinking water (sodium fluoride 100 ppm, corresponding to 37.8 ± 2.4 ppm F¯) for 70 days and administered with PBS or a probiotic strain, Lactobacillus johnsonii BS15 for 28 days prior to and throughout a 70 day exposure to sodium fluoride. Results showed that fluoride increases the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis and reduces the exploration ratio in novel object recognition (NOR) test and the spontaneous exploration during the T-maze test in mice following WAS, which were significantly improved by the probiotic. 16S rRNA sequencing showed a significant separation in ileal microbiota between the fluoride-treated mice and control mice. Lactobacillus was the main targeting bacteria and significantly reduced in fluoride-treated mice. BS15 reconstructed the fluoride-post microbiota and increased the relative abundance of Lactobacillus. D-lactate content and diamine oxidase (DAO) activity, two biomarkers of gut permeability were reduced in the serum of probiotic-inoculated mice. ZO-1, an intestinal tight junction protein was reduced by fluoride in mRNA, and its protein levels were increased by the probiotic treatment. Moreover, the hippocampus which is essential to learning and memory, down-regulated mRNA level of both the myelin-associated glycoprotein (MAG), and protein levels of brain-derived neurotrophic factor (BDNF), including the improvement of cAMP response element-binding protein (CREB) by BS15 in fluoride-exposed mice after WAS. Via spearman correlation analysis, Lactobacillus displayed significantly positive associations with the behavioral tests, levels of nerve development related factors, and intestinal tight junction proteins ZO-1, and negative association with TNF-α of the hippocampus, highlighting regulatory effects of gut bacteria on memory potential and gut barrier. These results suggested the psychoactive effects of BS15 on fluoride-induced memory dysfunction after psychological stress. In addition, there may be some correlations between fluoride-induced memory dysfunction and reconstruction of gut microbiota. AVAILABILITY OF DATA AND MATERIALS: 16S rRNA sequencing reads have uploaded to NCBI. The accession code of 16S rRNA sequencing reads in the National Center for Biotechnology Information (NCBI) BioProject database: PRJNA660154.


Assuntos
Fluoretos/metabolismo , Microbioma Gastrointestinal/fisiologia , Probióticos/farmacologia , Animais , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Lactobacillus/metabolismo , Masculino , Memória , Transtornos da Memória/induzido quimicamente , Camundongos , Microbiota , Sistema Hipófise-Suprarrenal/metabolismo , RNA Ribossômico 16S/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
15.
J Orthop Surg Res ; 16(1): 29, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422119

RESUMO

BACKGROUND AND HYPOTHESIS: The typical anterolateral approach is widely used to treat proximal humerus fractures with lateral locking fixation. However, lateral fixation cannot completely avoid medial reduction loss and varus deformity especially in the cases of an unstable medial column. We present a novel medial surgical approach and technique together with a minimally invasive lateral locking plate to fix proximal humerus fractures with an unstable medial column. MATERIALS AND METHODS: We performed an anatomical study and reported 8 cases of proximal humerus fractures with unstable medial columns treated with plate fixation through a minimally invasive anterolateral approach and medial approach. All surgeries were performed by the same single surgeon. Patients were followed clinically and radiographically at 1, 3, 6, and 12 months postoperatively. RESULTS: There was a safe region located at the medial part of the proximal humerus just beneath the articular surface. An anatomical medial locking proximal humerus plate could be placed in the medial column and did not affect the axillary nerve, blood supply of the humeral head, or stability of the shoulder joint. Successful fracture healing was achieved in all 8 cases. The function and range of motion of the shoulder joint were satisfactory 24 months postoperatively, with an average Constant score (CS) of 82.8. No reduction loss (≥ 10° in any direction), screw cutout, nonunion, or deep infection occurred. CONCLUSIONS: The combined application of medial anatomical locking plate fixation and minimally invasive lateral locking plate fixation is effective in maintaining operative reduction and preventing varus collapse and implant failure in proximal humerus fractures with an unstable medial column.


Assuntos
Placas Ósseas , Fixação Interna de Fraturas/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Fraturas do Ombro/cirurgia , Idoso , Feminino , Seguimentos , Consolidação da Fratura , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Fraturas do Ombro/fisiopatologia , Articulação do Ombro/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
16.
Orthop Surg ; 12(5): 1478-1488, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32975042

RESUMO

OBJECTIVE: To investigate the clinical efficacy and outcomes of the coracoid osteotomy with or without Bristow-Latarjet procedures in the treatment of chronic anterior shoulder dislocation (CASD). METHODS: Between January 2013 and January 2019, 20 shoulders of 18 patients who were diagnosed with chronic anterior dislocation and underwent open reduction in our trauma center were retrospectively studied. Open coracoid osteotomy with Bristow-Latarjet procedures were performed on 16 shoulders and open coracoid osteotomy without Bristow-Latarjet procedures were performed on four shoulders. Open coracoid osteotomy with or without Bristow-Latarjet procedures were chosen on the basis of the stability of the shoulder after reduction. Outcomes were assessed preoperatively and postoperatively with the visual analog scale (VAS) for pain, the American Shoulder and Elbow Surgeons (ASES) score, the University of California Los Angeles (UCLA) shoulder rating scale, and the range of motion (ROM) for shoulder activity. RESULTS: There were three males and 15 females with an average age of 60.94 ± 2.69 years. The time between dislocation and treatment ranged from 21 to 240 days with an average of 73.3 ± 14.4 days. All patients were available for a mean follow-up of 15.2 ± 4.3 months. No procedure-related death or incision-related superficial or deep tissue infection was identified in all cases. No iatrogenic neurovascular injuries or fractures were found in this study. At the time of 12 months follow-up, the range of motion and the shoulder functional evaluation (VAS [P < 0.001], ASES [P < 0.001], and UCLA score [P < 0.001]) in patients who underwent Bristow-Latarjet procedures were significantly improved. Subluxation after surgical procedure was found and confirmed in one patient and this patient refused to undergo revision surgery. According to the Samilson and Prieto classification system, 16 shoulders were assessed as grade 0, three shoulders were grade 1, one shoulder was grade 2. CONCLUSIONS: Coracoid osteotomy with or without Bristow-Latarjet procedure yielded an acceptable clinical result in this study. This method has the advantages of enlarging the exposure of surgical field, assisting reduction of shoulder, and convenient conversion to Bristow-Latarjet procedure. It is an efficient and reliable method for treatment of chronic anterior shoulder dislocation. A 69-year-old woman diagnosed with right chronic anterior shoulder dislocation with large Hill-Sachs lesion. The latarjet procedure with remplissage technique was applied for this patient.


Assuntos
Processo Coracoide/cirurgia , Procedimentos Ortopédicos/métodos , Osteotomia/métodos , Luxação do Ombro/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Amplitude de Movimento Articular , Estudos Retrospectivos , Inquéritos e Questionários
17.
J Bone Joint Surg Am ; 101(9): e36, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31045672

RESUMO

BACKGROUND: Partial traumatic hemipelvectomy (THP) is a catastrophic and life-threatening injury caused by high-energy impact. With advances in prehospital resuscitative techniques, more patients now survive this disastrous injury; however, the management of partial THP still lacks well-established therapeutic protocols. The purpose of this study was to present our experience in managing partial THP in a level-I trauma center. METHODS: We retrospectively reviewed the medical records of 21 consecutive patients with partial THP. The key points of successful treatment are hemorrhage control, proper decision-making regarding amputation, treatment of associated injuries, and infection control. Data on patient demographics, injury characteristics, surgical management, and outcomes were recorded and analyzed. RESULTS: Eight female and 13 male patients with a mean age of 31.3 years met the diagnostic criteria. The mean follow-up was 51.9 months. Of 17 surviving patients, 7 underwent primary amputation; limbs were successfully preserved in 4; and 6 patients underwent secondary amputation because of infection, organ dysfunction, and limb necrosis. Two patients died during resuscitation, and 2 patients died after amputation. Phantom limb pain, infection, and skin flap necrosis were the major postoperative complications. CONCLUSIONS: THP requires cooperative multidisciplinary emergency diagnosis and treatment, early surgical intervention, and definitive treatment. Rapid resuscitation, adequate hemostasis, early amputation, and repeated debridement may improve survival. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Amputação Traumática/cirurgia , Hemipelvectomia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Amputação Traumática/mortalidade , Tomada de Decisão Clínica , Protocolos Clínicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Centros de Traumatologia , Resultado do Tratamento , Adulto Jovem
18.
Med Sci Monit ; 22: 2295-300, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27367975

RESUMO

BACKGROUND The aim of this study was to explore the efficacy of temporary balloon occlusion of the abdominal aorta assisting open reduction and internal fixation (ORIF) in the treatment of complex acetabular fracture. MATERIAL AND METHODS From August 2000 to October 2011, a total of 48 patients with complex acetabular fracture were enrolled in this study. Average operative time, intraoperative blood loss volume, blood transfusion volume, satisfactory reduction, and postoperative functional recovery rate were recorded and compared between the 2 groups. RESULTS A significant difference was observed between the 2 groups in operative time (P=0.003). For intraoperative blood loss and blood transfusion, ORIF combined with temporary balloon occlusion of abdominal aorta techniques appeared to be superior to normal ORIF (blood loss: P=0.007; and blood transfusion: P=0.019, respectively). However, no differences were observed in postoperative blood loss or transfusion (P>0.05). Patients in group A showed better hip function than those in group B (group A: a good-to-excellent rate of 77.8%; group B: a good-to-excellent rate of 78.3%; P>0.05). With regard to the incidence of postoperative complications, there were no significant differences between the 2 groups (group A: 9/18; group B: 11/23; P=0.890). CONCLUSIONS In the treatment of complex acetabular fracture, temporary balloon occlusion of the abdominal aorta is a reliable technique to assist ORIF surgery to staunch the flow of blood.


Assuntos
Acetábulo/cirurgia , Aorta Abdominal/cirurgia , Oclusão com Balão/métodos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Acetábulo/lesões , Adulto , Perda Sanguínea Cirúrgica , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
19.
Stem Cells Int ; 2016: 7532798, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26977159

RESUMO

Oxidative stress induces bone loss and osteoporosis, and epigallocatechin-3-gallate (EGCG) may be used to combat these diseases due to its antioxidative property. Herein, oxidative stress in human bone marrow-derived mesenchymal stem cells (BM-MSCs) was induced by H2O2, resulting in an adverse effect on their osteogenic differentiation. However, this H2O2-induced adverse effect was nullified when the cells were treated with EGCG. In addition, treatment of BM-MSCs with EGCG alone also resulted in the enhancement of osteogenic differentiation of BM-MSCs. After EGCG treatment, expressions of ß-catenin and cyclin D1 were upregulated, suggesting that the Wnt pathway was involved in the effects of EGCG on the osteogenic differentiation of BM-MSCs. This was also confirmed by the fact that the Wnt pathway inhibitor, Dickkopf-1 (DKK-1), can nullify the EGCG-induced enhancement effect on BM-MSC's osteogenic differentiation. Hence, our results suggested that EGCG can reduce the effects of oxidative stress on Wnt pathway in osteogenic cells, which supported a potentially promising therapy of bone disorders induced by oxidative stress. Considering its positive effects on BM-MSCs, EGCG may also be beneficial for stem cell-based bone repair.

20.
Medicine (Baltimore) ; 94(37): e1491, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26376389

RESUMO

The aim of this study was to evaluate the potential advantages and clinical results of a modified minimally invasive ilioinguinal approach for the treatment of acetabular or pelvic fractures to the results obtained using a standard ilioinguinal approach. Forty-six patients who were diagnosed as having anterior column acetabular fractures or anterior pelvic ring fractures underwent open reduction and internal fixation through 2 different surgical approaches between June 2008 to June 2012 in our trauma center was studied. The modified ilioinguinal group included 20 patients and the other 26 patients were in the standard ilioinguinal approach group. The clinical and radiographic results were recorded and compared between the 2 groups. There were no significant differences between 2 groups in the mean age, sex, fractures type, and causes of acetabular or pelvic fractures. The mean blood loss in the modified group was 560.0 ±â€Š57.3 mL versus 850.0 ±â€Š59.0 mL in the standard ilioinguinal group. The operative time was significantly reduced with modified ilioinguinal approach (86.0 ±â€Š4.56 min vs. 101.9 ±â€Š5.38 min). The mean hospital stay was 16.8 ±â€Š0.58 days and 18.7 ±â€Š0.52 days in the modified and standard ilioinguinal groups, respectively. According to the Matta score, the quality of reduction between the 2 groups was not significantly different. The complication rate was low in the modified group but not significantly different between the 2 groups. Forty-two patients were followed up with clinical examination and radiographs at a mean of 15.2 months. Solid union was observed in 42 cases at a mean time of 14.8 weeks. The mean Harris Hip Score and the Majeed scores at the time of evaluation were not significantly different between the 2 groups. On comparing the 2 surgical ilioinguinal approaches, it was found that using modified ilioinguinal approach decreased operative time and blood loss, and did not affect the quality of fracture reduction and fracture healing. This study demonstrates that the modified ilioinguinal approach is a simple and minimally invasive approach for anterior column acetabular fractures and pubic rami fractures comparing with the standard ilioinguinal approach.


Assuntos
Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Ossos Pélvicos/lesões , Adulto , Feminino , Fixação Interna de Fraturas/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/estatística & dados numéricos , Estudos Retrospectivos
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